Skin tissue may be subject to many forms of damage, including burns, trauma, depigmentation (e.g., vitiligo), and the like. Grafts are often used to repair such skin damage. However, grafting techniques generally involve a large amount of tissue being removed from a donor site, preferably from the patient, and/or expensive and complex cultivation procedures using laboratory facilities to form larger portions of graft tissue from smaller donor samples.
For example, many people exhibit a condition known as vitiligo which results in depigmented regions of skin that may be aesthetically undesirable. Such depigmentation can cause a psycho-social stigma, especially in darker skinned individuals. Vitiligo affects about 1-4% of the population, including an estimated 1 to 2 million Americans. It affects both males and females of all races and ages.
Melanin is a pigment which gives skin its characteristic color. It is produced by certain skin cells called melanocytes. Vitiligo results when melanocytes either die or stop producing melanin. This condition may begin as small patches of lightened or whitened skin that can spread and grow larger with time. The depigmentation may occur cyclically, with periods of no change followed by periods of further pigment loss. The regions of depigmented skin tend to be irregular, and are more noticeable on people having darker skin. The exact cause of vitiligo is presently unknown, but it is believed to be associated with an autoimmune reaction.
Stable vitiligo generally refers to a vitiligo condition in which the lesions are not noticeably increasing in size or number over an extended observation period (e.g., days or weeks or longer). Present treatments for stable vitiligo have limited effectiveness. Such treatments can include oral medications or topical creams containing corticosteroid compounds. Ultraviolet therapy based on exposure to, e.g., UV-A or UV-B radiation combined with application of psoralen (a photosensitizer) may also be used. Temporary darkening of the depigmented areas can also be achieved by application of tinted cosmetics or dyes that color the skin. Another option is to permanently remove pigment in the surrounding normally-pigmented skin to achieve homogenous skin tone is possible by topical application of a compound containing 20% monobenzyl ether of hydroquinone. This therapy generally takes about a year to complete, and the pigment removal is permanent.
Autografting procedures in which a patient's own melanocytes are applied to the depigmented areas are another treatment technique for vitiligo. Culturing of melanocytes and transplanting them to depigmented areas can result in uniform repigmentation, but such autografting techniques can be cumbersome, expensive, time-consuming and/or require advanced laboratory facilities. A recent commercial version of this approach uses a harvesting device and bioenzymes to disperse melanocytes prior to autografting. This treatment can be expensive and often introduces enzymes which may not be desirable.
Sheet grafts can provide an improved appearance of the repaired tissue site and have been used, for example, to treat vitiligo. For example, sheet grafts may be used on large areas of the face, neck and hands, so that these more visible parts of the body can appear less scarred after healing. A sheet graft may be used to cover an entire depigmented or damaged region of skin, e.g., if the damaged site is small. Small areas of a sheet graft can be lost after placement because a buildup of fluid (e.g., a hematoma) can occur under the sheet graft following placement the sheet graft.
Sheet grafts may be full-thickness or split-thickness. A conventional split-thickness graft can be formed, e.g., by harvesting a sheet of epidermis and upper dermal tissue from a donor site, in a procedure similar to that of peeling an apple. The split-thickness graft can then be placed on the location of the burn or ulcer. The skin tissue may then grow back at the donor site following a generally extended healing time. Split-thickness grafts may be preferable to full-thickness grafts because removing large amounts of full-thickness skin tissue from the donor site can lead to scarring and extensive healing times at the donor site, as well as an increased risk of infection. However, skin tissue removed from the donor site for a split-thickness skin autograft may include both the epidermis and a portion of the dermis, which can lead to some scarring and/or dispigmentation (e.g., hyper- or hypo-pigmentation) at the donor site.
Another conventional technique that may be used to treat skin pigmentation defects can be referred to as “non-cultured autologous melanocyte transplantation.” In this technique, harvested graft tissue can be dissociated using either an enzymatic digestion process (e.g., by treating the tissue with trypsin or the like), or by mechanically grinding the tissue to form a paste-like substance. The resulting cell solution can then be transplanted onto a dressing (e.g., a conventional dressing, a collagen bandage, etc.) and the dressing then applied to the affected area. However, grafts formed using such techniques may not be well-controlled and/or reproducible. Processing of the graft tissue in such techniques can also produce cellular trauma, which can reduce the effectiveness of the applied grafts.
Burns are another common form of skin trauma which may be treated by autografting. Large areas of skin may be damaged by burns, which generally require removal of larger areas of tissue from donor sites to repair them. Repair of burned tissue is often based on providing tissue containing viable keratinocytes to the burned area. Proliferation of the keratinocytes can help to regrow skin tissue and repair the damaged areas.
Another autografting approach is blister grafting, in which blisters are created on pigmented skin using suction. The raised blisters are then cut off and transplanted to depigmented skin areas, where blisters of the same size have been formed and removed. This technique generally requires the extensive use of donor sites having substantially the same area as the depigmented regions being treated. An exemplary blister grafting technique, in which small graft strips formed from raised blisters are transferred to a dermabraded recipient site, is described in S. S. Awad, Dermatol Surg, 34:9 (September 2008), 1186-1193. The Awad article also describes various devices used to form suction blisters.
Another autografting technique is “mini-punch” autografting, where mini-punch biopsies are taken from the donor area. Same-sized mini-punch biopsies are taken from the recipient depigmented sites and replaced by the donor area mini-punch grafts. This technique often results in a “cobblestone” appearance at the recipient site, and also may result in some scarring at the donor site. Mini-punch autografting may also not be effective for repigmenting large areas.
Still another conventional technique that may be used for autografting of tissue, often referred to in the literature as the “Meek technique,” includes removal of a region of graft tissue from a donor site, cutting the graft tissue into micrografts—each having a size on the order of millimeters, applying the cut graft tissue onto a piece of prefolded gauze, and unfolding the gauze to separate the individual micrografts by a desired separation distance. The expanded gauze containing the separated micrografts can then be applied to a wound site to allow the micrografts to grow into the tissue at the wound site. After several days, the gauze may be removed and an allograft overlay or the like can be applied over the micrografts. Such technique is described, e.g., in R. W. Kreis et al., Burns, 20 (1) (1994), S39-S42, and in A. R. Lari et al., Burns, 27, (2001), 61-66. The Meek technique can be limited by the relatively large size of the micrografts used, which may lead to a nonuniform appearance of the skin, and the use of gauze that is prefolded in a particular configuration that determines the subsequent separation distances of the micrografts.
Another autografting technique, described in S. V. Mulekar et al., Dermatol Surg, 35:1 (January 2009), 66-71, includes formation of a centrifuged suspension of cells obtained from a superficial portion of a donor site. This suspension is then applied over a larger recipient site that has been abraded, and then covered with a dry collagen film.
Accordingly, there is a need for improved methods and apparatus for repairing skin tissue, such as treating vitiligo by repigmenting regions of skin or healing burns, which is long-lasting, relatively simple and inexpensive, and effective. Such methods and apparatus preferably do not require enzymes or expensive and complex laboratory facilities and cell cultures, and would preferably be capable of repairing relatively large areas of tissue without needing removal of large portions of skin from donor sites.